Acid-Catalyzed Cascade Ring-Opening and Addition Reactions of Arylvinylcyclopropenes with r,β-Unsaturated Substrates, Scope and Limitations Zhi-Bin Zhu‡ and Min Shi*,†,‡ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032 China, and Laboratory for AdVanced Materials and Institute of Fine Chemicals, East China UniVersity of Science & Technology, 130 Meilong Road, Shanghai 200237, People’s Republic of China
[email protected] ReceiVed December 21, 2008
Catalyzed by Al(III) catalyst, arylvinylcyclopropenes react with R,β-unsaturated substrates smoothly to produce the Diels-Alder adducts in moderate to good yields through a cascade ring-opening reaction/ Diels-Alder cycloaddition. On the other hand, strong Brønsted acid TfOH can promote the cascade intramolecular Friedel-Crafts/1,4-addition reaction to produce indene derivatives in moderate to good yields under mild conditions. The acidity of the catalysts plays a key role in these reactions.
Introduction 1
Cyclopropenes, as highly strained small ring species, have been of continuing interest in the past few decades.2 One of the most common behaviors of cyclopropenes is the ringopening reaction under various conditions. For example, photoirradiation3 of 1,2-diphenyl-3,3-dimethylcyclopropene produced the isomeric dienes in a 3:l ratio (Scheme 1, reaction a).4 Moreover, thermolysis of tetramethylcyclopropene at 490 * Corresponding author. Fax: 86-21-64166128. ‡ East China University of Science & Technology. † Chinese Academy of Sciences. (1) For a review, see: Baird, M. S. Cyclopropenes: Synthesis: By Construction of the System. Houben-Weyl; Thieme: Stuttgart, Germany, 1997; E17d/2, p 2695. (2) For reviews, see: (a) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. ReV. 2007, 107, 3117. (b) Rubin, M.; Rubina, M.; Gevorgyan, V. Synthesis 2006, 1221. (c) Fox, J. M.; Yan, N. Curr. Org. Chem. 2005, 9, 719. (d) Walsh, R. Chem. Soc. ReV. 2005, 34, 714. (e) Dolbier, W. R., Jr.; Battiste, M. A. Chem. ReV. 2003, 103, 1071. (f) Sekiguchi, A.; Lee, V. Y. Chem. ReV. 2003, 103, 1429. (g) Chen, K.-C.; Lee, G.-A. Huaxue 2006, 64, 73. (h) Baird, M. S. Chem. ReV. 2003, 103, 1271. (3) For a review of excited state chemistry of cyclopropenes, see:Padwa, A. Acc. Chem. Res. 1979, 12, 310. (4) Arnold, D. R.; Pincock, J. A.; Morchat, R. J. Am. Chem. Soc. 1973, 95, 7536.
10.1021/jo802786r CCC: $40.75 2009 American Chemical Society Published on Web 02/23/2009
or 260-298 °C led to dimethylpenta-1,3-dienes (Scheme 1, reaction b).5 Alternatively, if there is no methyl group or only one methyl group at the C-3 position, the pyrolysis of cyclopropenes afforded alkyne products (Scheme 1, reactions c and d).6 Furthermore, Brønsted acid (TsOH) could promote the ringopening reaction of cyclopropene to afford the corresponding 1,3-diene product when the β-cationic center is stabilized by the trimethylsilyl group (Scheme 1, reaction e).7 These ring-opening products give the probability that cyclopropenes can act as dienes to react with other dienophiles in a cascade reaction process with such ring-opening reaction followed by the Diels-Alder cycloaddition, which was different from the common roles of dienophiles that cyclopropenes acted in most cases.8 Namely, as common dienophiles, cyclopropenes can directly react with various dienes under mild conditions to give the corresponding formal Diels-Alder products, sixmembered rings with up to four stereogenic centers, in a regio(5) Selective examples of thermolysis of cyclopropenes, see: (a) Stechl, H.H. Chem. Ber. 1964, 97, 2681. (b) Srinivasan, R. J. Chem. Soc., Chem. Commun. 1971, 1041. (6) Srinivasan, R. J. Am. Chem. Soc. 1969, 91, 6250. (7) Padwa, A.; Wannamaker, M. W.; Dyszlewski, A. D. J. Org. Chem. 1987, 52, 4760.
J. Org. Chem. 2009, 74, 2481–2485 2481
Zhu and Shi SCHEME 1.
Ring-Opening Reactions of Cyclopropenes
FIGURE 1. ORTEP drawing of compound 3a. SCHEME 2. AlCl3-Catalyzed Cascade Ring-Opening Diels-Alder Reaction
and stereocontrolled way and in good yields.9 In this paper, we wish to report the acid-catalyzed regioselective ring-opening reaction of arylvinylcyclopropenes 110 followed by Diels-Alder cycloaddition with R,β-unsaturated substrates to construct cyclohexene skeletons, in which cyclopropenes acted as predienes rather than dienophiles to construct six-membered-ring compounds. Moreover by changing the catalyst to a stronger Brønsted acid, a cascade intramolecular Friedel-Crafts/1,4addition of 1 with R,β-unsaturated substrates took place to produce indene derivatives under identical conditions. Results and Discussion To obtain the ring-opening products of phenylvinylcyclopropene 1a, we initially attempted pyrolysis of 1a at 260 °C, but it was found that none of the corresponding ring-opening product 4a was formed. Furthermore, by adding maleic anhydride 2a under the same condition to trap the in situ formed 4a, we found that complicated reaction products were obtained, presumably due to both of the reactants and the products are being stable at such high temperature. Then, using 0.1 equiv of AlCl3 as the catalyst, it was found that the Diels-Alder cycloaddition product 3a, derived from the reaction of ring-opening product 4a (the E-configuration of 4a was deduced by the retro-D-A reaction of endo-adduct 3a) with 2a, was obtained in 80% yield along with the rearrangement product 6a in 16% yield at 70 °C in 1,2-dichloroethane (DCE). In addition, the product 3a did not undergo further Diels-Alder cycloaddition with another molecule of 2a, presumably due to the steric hindrance of the two adjacent phenyl groups (Scheme 2). Compound 3a was unam-
TABLE 1.
Ring-Opening Reaction of 1a in the Presence of Various Lewis or BrOnsted Acids
yield (%)b entrya
cat.
solvent
T (°C)
1 2 3 4 5 6 7 8 9 10 11
AlCl3 AlCl3 CH3CO2H HCl ZrCl4 TsOH TsOH cat. Al(III) cat. Al(III) cat. Al(III) cat. Al(III)
DCE DCE DCE DCE DCE DCE DCE DCE toluene DCM THF
20 70 70 70 70 20 70 70 70 20 70
4a
5a
6a
49
35
14
56
39 88 25 39
10
57 40
97 92 17
a
(8) For examples, see: (a) Law, D. C. F.; Tobey, S. W. J. Am. Chem. Soc. 1968, 90, 2376. (b) Deem, M. L. Synthesis 1972, 675. (c) Battiste, M. A. Tetrahedron Lett. 1964, 3795. (d) Closs, G. L. In AdVances in Alicyclic Systems; Hart, H., Karabatsos, G. J., Eds.; Academic Press: New York, 1966; pp 53127. (e) Apeloig, Y.; Arad, D.; Kapon, M.; Wallerstein, M. Tetrahedron Lett. 1987, 28, 5917. (f) Battiste, M. A.; Posey, R. G. J. Fluorine Chem. 2000, 102, 285. (g) Muller, P.; Bernardinelli, G.; Rodriquez, D.; Pfyffer, J.; Schaller, J.-P. Chimia 1987, 41, 244. (h) Muller, P.; Bernardinelli, G.; Pfyffer, J.; Rodriquez, D.; Schaller, J.-P. HelV. Chim. Acta 1988, 71, 544. (i) Magid, R. M.; Wilson, S. E. J. Org. Chem. 1971, 36, 1775. (j) Battiste, M. A.; Sprouse, C. T., Jr. Tetrahedron Lett. 1970, 4661. (k) Muller, P.; Bernardinelli, G.; Pfyffer, J.; Schaller, J.-P. HelV. Chim. Acta 1991, 74, 993. (l) Battiste, M. A.; Kapicak, L. A.; Mathew, M.; Palenik, G. J. Chem. Commun. 1971, 1536. (9) Fringuelli, F.; Taticchi A. The Diels-Alder Reaction: Selected Practical Methods; Wiley: New York, 2002; p 1. (10) (a) Shao, L.-X.; Zhang, Y.-P.; Qi, M.-H.; Shi, M. Org. Lett. 2007, 9, 117. (b) Shi, M.; Jiang, M.; Liu, L.-P. Org. Biomol. Chem. 2007, 5, 438.
2482 J. Org. Chem. Vol. 74, No. 6, 2009
All reactions were carried out with 1a (0 0.2 mmol) in the presence of the listed catalysts (10 mol %) and solvent (1.0 mL). b Isolated yields.
biguously determined by an X-ray diffraction (Figure 1) and its CIF data are presented in the Supporting Information.11 To determine the optimal conditions of the ring-opening reaction of 1a, we carried out the reactions of 1a in the presence (11) The crystal data of 3a have been deposited in CCDC with the number 679736. Empirical formula: C33H32O5; formula weight: 508.59; crystal color, habit: colorless, prismatic; crystal dimensions: 0.457 × 0.411 × 0.347 mm; crystal system: Monoclinic; lattice type: primitive; lattice parameters: a ) 16.4843(15) Å, b ) 9.9238(9) Å, c ) 16.6985(16) Å, R ) 90°, β ) 106.622(2)°, γ ) 90°, V ) 2617.5(4) Å3; space group: P2(1)/c; Z ) 4; Dcalc ) 1.291 g/cm3; F000 ) 1080; diffractometer: Rigaku AFC7R; residuals: R ) 0.0900, Rw ) 0.2676.
Acid-Catalyzed Reactions of ArylVinylcyclopropenes TABLE 2.
b
Scope of the Cascade Ring-Opening and Diels-Alder Cycloaddition
a All reactions were carried out with 1 (0.2 mmol) and 2 (0.3 mmol) in the presence of Al-catalyst (0.02 mmol) and DCE (2.0 mL) at 70 °C for 24 h. Isolated yields. c 2 (2 mmol) was used.
of various Lewis and Brønsted acids. At room temperature, no reaction occurred in the presence of AlCl3 in DCE (Table 1, entry 1). At 70 °C, 4a was provided in 49% yield along with the rearrangement product 1,4-diphenyl-2-(propan-2-ylidene)1,2-dihydronaphthalene 5a in 35% yield and naphthalene derivative 6a in 14% (Table 1, entry 2). The structure of 5a was further confirmed by X-ray diffraction and its CIF data are presented in the Supporting Information.12 With acetic acid as the catalyst at 70 °C, no reaction occurred (Table 1, entry 3). Brønsted acid HCl did not produce 4a, affording 5a and 6a in 56% and 39% yield, respectively (Table 1, entry 4). Using ZrCl4 as the catalyst provided naphthalene derivative 6a exclusively in 88% yield, which is very similar as that catalyzed by BF3 · OEt2 (Table 1, entry 5).10 Using Brønsted acid TsOH as the catalyst afforded 4a in 10% yield along with 57% of 5a and 25% of 6a at 20 °C (Table 1, entry 6). On the other hand, 5a and 6a were formed in 40% and 39% yield, respectively, at 70 °C without the formation of 4a, which is significantly (12) The crystal data of 5a have been deposited in CCDC with the number 672065.
different from those reactions shown in Scheme 1 since substrate 1a does not have a TMS group to stabilize the cationic intermediate13 (Table 1, entry 7). Interestingly, although we could not obtain 4a in 80% yield when AlCl3 was used as the catalyst (80% of 3a was formed as shown in Scheme 2), it was found that using AlCl3 hydrolyzed Al(III) powder14 as the catalyst [indicated as cat. Al(III) in this paper] produced 4a in 97% yield in DCE at 70 °C exclusively (Table 1, entry 8). In toluene, 4a was formed in 92% yield under the standard conditions (Table 1, entry 9). The examination of solvent effects revealed that DCE is the best one for the reaction to give the corresponding ring-opening product 4a exclusively in higher yield (Table 1, entries 8-11). (13) Colvin, E. W. Chem. Soc. ReV. 1978, 7, 15. (14) We also found that the AlCl3 used in Scheme 2 was partially hydrolyzed by water, but if using Al(OH)3 as the catalyst, no reaction occurred along with the recovery of the starting materials 1a. Therefore, we found that Al(III) complex [Al(OH)2Cl]n, which was prepared by partial hydrolysis of AlCl3 with water, is the effective catalyst in this reaction. See the Supporting Information for the details. (15) The crystal data of 7a have been deposited in CCDC with the number 687327.
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Zhu and Shi TABLE 3.
TfOH-Catalyzed Reactions of 1 with 2f-h
a All reactions were carried out with 1 (0.2 mmol) and 2 (0.6 mmol) in the presence of TfOH (0.02 mmol) and DCE (2.0 mL) at 70 °C for 24 h. b Isolated yields.
With the best reaction conditions in hand, we next examined the cascade ring-opening and Diels-Alder cycloaddition of a variety of arylvinylcyclopropenes 1 with R,β-unsaturated substrates 2 and the results of these experiments are summarized in Table 2. The reactions of 1a with 2a, 1-phenyl-1H-pyrrole2,5-dione 2b, and diethyl but-2-ynedioate 2c proceeded smoothly to give the corresponding D-A adducts 3a-c in good to excellent yields (Table 2, entries 1-3). As for unsymmetrical dienophiles 2d-f, regioisomeric mixtures 3 and 3′ were obtained in good to excellent yields (Table 2, entries 4-6). By using 2c as the dienophile to examine the reactions with other arylvinylcyclopropenes 1b-f, the corresponding D-A adducts 3b-f were obtained in good yields under the standard conditions (Table 2, entries 7-11). During the examination of the catalytic ability of Brønsted acids in this reaction, it was found that if the strong Brønsted acid trifluoromethanesulfonic acid (CF3SO3H, TfOH) was used as the catalyst, the naphthalene derivatives 7 were obtained via the cascade intramolecular Friedel-Crafts/1,4-addition process rather than the expected formal D-A cycloadducts or the ringopening products 4. For example, with methyl vinyl ketone 2f and acrylaldehyde 2g as the substrates to react with 1a in DCE in the presence of TfOH (10 mol%), naphthalene derivatives 7a and 7b were obtained in 70% and 15% yield, respectively (Table 3, entries 1 and 2). Arylvinylcyclopropenes 1c and 1e could also react with 2f to produce naphthalene derivatives 7c and 7d in moderate to good yields and since the substitutions on the aromatic rings are at the para position, only one product can be produced when the intramolecular Friedel-Craft reaction took place (Table 3, entries 3 and 4). As for cyclopent-2-enone 2h, the corresponding naphthalene derivative 7e was formed in 60% yield in the reaction with 1a (Table 3, entry 5). The structure of compound 7a was unambiguously determined by X-ray diffraction and its CIF data are presented in the Supporting Information (Figure 2).15 A plausible mechanism for the formation of cycloadducts 3 and conjugate addition products 7 is outlined in Scheme 3. Initially, the protonation of arylvinylcyclopropene 1 by acid (Al(III) catalyst or TfOH) produces intermediate A or A′ (path I or path II), which undergoes a ring-opening process to give intermediate B or C. Intermediate C can be converted to intermediate B via 1,2-proton transfer. Deprotonation of intermediate B produces 4, and followed by a Diels-Alder cycloaddition with 2 catalyzed by Al(III) catalyst to give D-A adduct 3. In the presence of strong Brønsted acid TfOH, intermediate B undergoes intramolecular isomerization to afford the corre2484 J. Org. Chem. Vol. 74, No. 6, 2009
FIGURE 2. ORTEP drawing of compound 7a. SCHEME 3.
A Plausible Reaction Mechanism
sponding 1,2-dihydronaphthalene derivative 5 other than deprotonation,10 which reacts with protonated R,β-unsaturated ketone or aldehyde to produce intermediate F. Isomerization of intermediate F gives the corresponding naphthalene derivative 7 (Scheme 3). It should be noted that it is impossible to prepare alkylvinylcyclopropenes (both R1 are alkyl groups or one R1 is an alkyl group) via the corresponding alkylvinylidenecyclopropanes by using our previously reported procedure since the corresponding enynes were produced exclusively (see the Supporting Information for details).10 In conclusion, we have found an interesting cascade reaction of ring-opening of arylvinylcyclopropenes followed by cycloor 1,4-addition with a variety of R,β-unsaturated substrates catalyzed by Brønsted acids, which affords an efficient synthetic protocol for the preparation of functionalized cyclohexene or indene derivatives. Further work directed at elucidation of the detailed mechanism of this process and the application of it to the synthesis of cyclohexene or indene containing natural products is currently in progress. Experimental Section General Procedure for the Preparation of Al(III) Catalyst [cat. Al(III): Al(OH)2Cl]. Water (10 mL) was added dropwise into aluminum chloride (4.0 g, 0.2 mmol) then the solution was dried by a blast oven. This catalyst was indicated as cat. Al(III) in this paper.
Acid-Catalyzed Reactions of ArylVinylcyclopropenes Al-Catalyzed Ring-Opening Diels-Alder Reaction of Arylvinylcyclopropenes 1a with Maleic Anhydride 2a. Under an argon atmosphere, 1,1-diphenyvinylcyclopropene (64 mg, 0.2 mmol), maleic anhydride 2a (30 mg, 0.3 mmol), and cat. Al(III) (2 mg, 0.02 mmol) were added into a Schlenk tube. The reaction mixture was stirred at 70 °C for 24 h to give 3a in 86% yield after column chromatography. TfOH-Catalyzed Reaction of Arylvinylcyclopropenes 1a with Methyl Vinyl Ketone 2f. Under an argon atmosphere, 1,1diphenyvinylcyclopropene 1a (64 mg, 0.2 mmol), methyl vinyl ketone 2f (50 µL, 0.6 mmol), and TfOH (2 µL, 0.02mmol) were added into a Schlenk tube. The reaction mixture was stirred at 70 °C for 24 h to give 7a in 70% yield after column chromatography. Compound 3a: white solid, mp 179-181 °C; IR (CH2Cl2) ν 3028, 2903, 2849, 1855, 1782, 1711, 1489, 1443, 1219, 1109, 999, 902, 769, 698, 588 cm-1; 1H NMR (300 MHz, CDCl3, TMS) δ 1.84 (3H, s, CH3), 2.49 (1H, dd, J1 ) 11.4 Hz, J2 ) 19.2 Hz, CH2), 2.88 (1H, d, J ) 19.2 Hz, CH2), 3.02 (1H, dd, J1 ) 7.2 Hz, J2 ) 9.9 Hz, CH), 3.24-3.31 (1H, m, CH), 3.66 (1H, d, J ) 7.2 Hz, CH), 6.46 (1H, s, CH), 6.88-6.91 (2H, m, Ar), 7.10-7.24 (10H, m, Ar), 7.34-7.37 (3H, m, Ar); 13C NMR (75 MHz, CDCl3, TMS) δ 20.6, 27.1, 37.5, 43.8, 45.7, 127.0, 127.6, 127.8, 127.9, 128.0, 128.1, 128.3, 128.6, 128.7, 129.5, 129.9, 131.5, 136.5, 140.4, 142.3, 143.8, 171.1, 173.7; MS (EI) m/z (%) 420 (43.73) [M+], 378 (31.55), 377 (100), 331 (26.09), 253 (28.80), 231 (69.29), 215 (26.46), 167 (37.70), 91 (38.02); HRMS (EI) calcd for C29H24O3 (M+) requires 420.1725, found 420.1723.
Compound 7a: white solid, mp 69-70 °C; IR (CH2Cl2) ν 3058, 3059, 3002, 2959, 1948, 1716, 1590, 1360, 1165, 1073, 1031, 892, 770, 730, 703 cm-1; 1H NMR (300 MHz, CDCl3, TMS) δ 1.22 (6H, s, CH3), 1.85 (2H, t, J ) 8.1 Hz, CH2), 2.04 (3H, s, CH3), 2.28 (2H, J ) 8.1 Hz, CH2), 7.12-7.54 (14H, m, Ar), 7.88 (1H, d, J ) 8.4 Hz, Ar); 13C NMR (75 MHz, CDCl3, TMS) δ 30.0, 31.3, 37.9, 40.0, 40.1, 125.3, 125.4, 125.5, 127.2, 127.3, 127.7, 127.8, 127.9, 128.3, 129.8, 130.2, 131.2, 134.8, 137.5, 139.5, 141.0, 141.1, 141.2, 209.1; MS (EI) m/z (%) 392 (71.12) [M+], 393 (24.65), 322 (31.68), 321 (100), 307 (13.47), 306 (29.67), 305 (13.74), 291 (40.65), 43 (13.76); HRMS (EI) calcd for C29H28O (M+) requires 392.2140, found 392.2132.
Acknowledgement. Financial support from the Shanghai Municipal Committee of Science and Technology (06XD14005 and 08dj1400100-2), National Basic Research Program of China (973)-2009CB825300, and the National Natural Science Foundation of China (20872162, 20672127, 20732008, 20821002, and 20702013) is greatly acknowledged. Supporting Information Available: Spectroscopic data of the compounds shown in Tables 1-3 and detailed descriptions of experimental procedures. This material is available free of charge via the Internet at http://pubs.acs.org. JO802786R
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